Friday, October 22, 2010

Researchers at the University of California, San Diego School of Medicine have identified the molecular mechanism that makes omega-3 fatty acids so effective in reducing chronic inflammation and insulin resistance…Advertisement

The discovery could lead to development of a simple dietary remedy for many of the more than 23 million Americans suffering from diabetes and other conditions.

Macrophages are specialized white blood cells that engulf and digest cellular debris and pathogens. Part of this immune system response involves the macrophages secreting cytokines and other proteins that cause inflammation, a method for destroying cells and objects perceived to be harmful. Obese fat tissue contains lots of these macrophages producing lots of cytokines. The result can be chronic inflammation and rising insulin resistance in neighboring cells over-exposed to cytokines. Insulin resistance is the physical condition in which the natural hormone insulin becomes less effective at regulating blood sugar levels in the body, leading to myriad and often severe health problems, most notably Type 2 diabetes.

Fasting and stress have opposite influences on the energy expenditure of the human organism. The healthy human body is capable of passing from a state involving three regular food intakes to a state of short-term fasting and even prolonged fasting, as a result of precise metabolic regulation. In these cases, the organism will save as much energy as possible, thus reducing energy expenditure.

However, in stress conditions, energy expenditure is markedly increased. As a result, the body´s metabolism will be converted into a catabolic state, the gravity of which is determined by the nature and degree of the injury and type and severity of underlying disease.

These and other processes will be developed in the following chapters.

[Table of contents]

4.1 Effects of fasting

In theory, if a person having 15 kg of adipose triglycerides — i.e. 140.000 kcal of reserves in the form of fats (Cahill, 1970)— and energy requirements of 1800 kcal/day, begins to fast, he should be capable of withstanding 75 days of total fasting. In practice, an abstinence from feeding leads to death after about 50 days of total fasting. In other words, the theoretical value of the energy reserves can not be used in its entirety, because death intervenes beforehand due to partial depletion of functional tissue proteins.

In the case of abstinence or fasting, endogenous energy stores are used for metabolic processes. Fat, stored in indifferent fat tissue, is the major source of energy. Energy can also be derived from protein; however, there is no indifferent protein tissue and as a consequence the loss of protein always leads to a loss of organ function.

Hence, in the case of fasting in healthy persons, the metabolism is aimed at keeping the loss of protein as low as possible by lowering the metabolism and the gluconeogenesis. The loss of nitrogen is reduced in the case of complete fasting from 10 g per day to 4 - 5 g a day after 3 weeks. Fat stores are depleted faster with the purpose of providing energy.

Many organs including the heart, kidneys and muscles, can use either fatty acids or ketone bodies, derived from partial oxidation of fatty acids, directly as energy substrates. The central nervous system, on the other hand, and the red blood cells can only use glucose as an energy substrate. For example, during a 24 hour fast, the brain will consume 150 g of glucose and the other organs about 36 g, i.e. a total of 186 g of glucose per day. Since the body is incapable of synthesizing glucose from fat, it uses other substrates for gluconeogenesis. In fact, the glycogen reserves are insufficient to cover the requirements for more than 1 day. The most important substrate for gluconeogenesis is provided by amino acids and, to a minor extent, by glycerol derived from the triglycerides.Metabolism of short-term fastingFig. 8: Metabolism of short-term fasting

In short-term fasting, some of the glucose required by the brain is provided by liver glycogen, the reserve being exhausted within 48 hours. If the human body is to withstand fasting, it must mobilize 1800 kcal/day and produce 186 g of glucose mainly for the central nervous system. Eighty percent of the energy requirements are provided by lipolysis of adipose tissue where 160 g of triglycerides are split into fatty acids and glycerol. Approximately 75 g of muscle proteins, i.e. nearly 300 g of muscle, per day are mobilized to provide the substrate for gluconeogenesis. If protein breakdown were to continue at the initial rate, roughly one-third of the total body proteins would be exhausted in 3 weeks, which is incompatible with survival.

So, if fasting is prolonged, a major metabolic adaptation occurs. The central nervous system begins to use ketone bodies as an energy substrate, thereby reducing glucose requirements. Therefore, in prolonged fasting, there is a shift from the use of protein as an energy source towards the use of fats (in the form of ketone bodies). This adaptation permits protein sparing and preserves the proteins' functional role. Nevertheless, obligatory proteolysis always persists, amounting in the foregoing example to at least 20 g of protein daily.Metabolism of short-term fastingFig. 9: Metabolism of prolonged fasting

Metabolic processes respond to internal signals. During fasting, blood glucose levels fall with a consequent reduction in the secretion of insulin and an increase in glucagon, two hormones with antagonistic actions on energy metabolism. As a result of the decrease in the circulating insulin level, triglyceride catabolism increases, causing the release of free fatty acids and glycerol. The raised glucagon levels lead initially to a distinct increase in liver glycogenolysis. Further, gluconeogenesis is stimulated by glucagon, which inhibits protein synthesis and stimulates muscular proteolysis, thereby furnishing the amino acid substrate.

There is therefore a metabolic adaptation to prolonged fasting, resulting in a reduction of energy expenditure of up to 40% (Goldstein and Elwyn, 1989; Kinney, 1970). These mechanisms, which tend to limit proteolysis in the healthy person, are defective or non-operative in cases of severe disease or stress, as will be discussed in the next chapter.

Thursday, October 21, 2010

"On the occasion of World Heart Day (September 26) there’s a bad news for vegetarians Indians. As per a new research report presented by a Pune-based bariatric Dr. Shashank Shah, vegetarian Indians are more prone to suffer from heart ailments.

Commenting on why veggie Indians are more at risk of heart diseases, Dr. Shah said in a press statement, “We found that Indians are grossly deficient in vitamin B12, which is a crucial cardio-protective factor in the body.

Vitamin B12 is usually found in food that comes from animals, like fish, meat, poultry, milk and milk products. However, since a lot of Indians are vegetarians, they do not get adequate amounts of vitamin B12 in their diet.”"

[...]

Details of research studyTo come to this startling conclusion Dr Shah along with his colleague Dr Todkar, studied the data collected from about 300 patients from Hiranandani Hospital, Powai, over the period of one year.

They were startled to find out that 70 percent of these patients had suffered from a cardiac [pertaining to the heart.] disease or are at greater risk of cardiac attack in near future.

Nearly all of them were found to be suffering from vitamin B12 deficiency.

“When vitamin B12 levels fall, homocysteine levels increase. The latter is known to cause atherosclerosis (hardening and narrowing of the arteries), as well as an increased risk of heart attacks, strokes and blood clot formation,” noted Dr Shah in his study report.

1 From the Department of Nutrition, University of California, Davis, CA (DAM); INSERM ERI-12, UFR de Médecine et de Pharmacie, Université de Picardie Jules Verne, Amiens, France (TBD); and the Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA (EMS).

For the past 3 decades, the US government has promoted a policy of reduced dietary sodium intake as the principal nutritional means of reducing blood pressure and its attendant cardiovascular disorders in adults. Early on, this policy targeted at-risk individuals such as people with chronic arterial hypertension; however, in the past decade it has been applied to the population at large. Despite a litany of well-intended strategies from mandatory sodium labeling to extensive educational and social marketing efforts, there is little evidence that sodium intake has changed. In fact, some advocates of the policy have argued that sodium intake actually has increased, reaching extreme levels in some people (1). The failure of the government's efforts has been typically attributed to the food industry's excessive use of sodium in their products (1). Both the application of such a government policy to the entire population and the simplistic assessment that its failure to date can be attributed to the food industry's reluctance to provide lower sodium foods belie the scientific complexity of the issues, including sodium's role in health and disease.

In this issue of the Journal, Bernstein and Willett (2) provide a valuable analysis of 24-h urinary sodium (UNaV) data extracted from the medical literature published between 1957 and 2003. Their findings from the 38 US studies that met rigorous search criteria and involved 26,271 people confirm and extend the conclusions we published a year ago (3). Our analysis involved 19,151 people from 33 countries and 62 survey sites between 1984 and 2008. Like that of Bernstein and Willett, our analysis revealed a remarkably narrow range of UNaV across very diverse populations and eating habits, without the extreme levels often purported to exist by advocates of lower sodium intake (1) and no evidence of a change over time. The latter was best shown by the data of the UK Food Standards Agency between 1986 and 2008, which we noted (3) offered no evidence that an intense social marketing effort begun in 2005 had been successful.

One possible explanation, first raised by our report last year (3), is that human sodium intake is a parameter that even the most well intentioned public policy cannot modify in most people. An extensive body of basic science research, dating from Richter's seminal observations (4), has characterized an integrated network of peripheral hormonal signals interfaced with complex neural networks specific to regulating sodium intake of experimental animals (5). Although those basic research findings have not as yet been extrapolated to humans, they should not be completely ignored because they may yet provide a model of what is feasible in humans.

The current report extends our observations by documenting that, likewise, all the efforts in the United States over the past 3 decades have had no effect on the population's sodium intake. An alternative possibility for the stability of sodium intake is that sodium has been largely consumed in association with food intake, motivated by hunger and appetite. To the extent that caloric intake has been stable over populations and decades, so too has sodium. Thus, a potential benefit of reducing food sodium content would be a concurrent reduction of sodium. Working against that theoretical outcome, however, is the reality that over the millennia, before the introduction of processed foods, sodium was added to foods at the time of preservation, cooking, or consumption. An individual in our society has the identical options today as the food industry moves to offering more products whose ratio of calories to sodium is increased (ie, lower sodium content per serving). This individual choice could abrogate any effect on average sodium intake in society as these data indicate has happened.

Regardless of why sodium intake has been so stable, the data of Bernstein and Willett (2), as well those of McCarron et al (3), suggest that it is not a readily modifiable nutritional parameter for the population at large. Furthermore, a substantial body of research in humans provides evidence as to why this latest attempt to modify the general population's sodium intake is doomed to failure. Sodium has a critical role in extracellular fluid volume regulation as well as being of fundamental importance in cellular function across virtually all organ systems. Thus, it is unlikely that as an organism, humans would have evolved without the development of failsafe mechanisms to ensure sufficient sodium availability. Sodium is 1 of only 3 nutrients whose excretion in urine is recognized as regulated; water and glucose are the other 2. Consequently, deficits in these nutrients elicit immediate, potent, counterregulatory physiologic responses.

Low-fat diets have been shown to increase plasma concentrations of lipoprotein(a) [Lp(a)], a preferential lipoprotein carrier of oxidized phospholipids (OxPLs) in plasma, as well as small dense LDL particles. We sought to determine whether increases in plasma Lp(a) induced by a low-fat high-carbohydrate (LFHC) diet are related to changes in OxPL and LDL subclasses. We studied 63 healthy subjects after 4 weeks of consuming, in random order, a high-fat low-carbohydrate (HFLC) diet and a LFHC diet. Plasma concentrations of Lp(a) (P < 0.01), OxPL/apolipoprotein (apo)B (P < 0.005), and OxPL-apo(a) (P < 0.05) were significantly higher on the LFHC diet compared with the HFLC diet whereas LDL peak particle size was significantly smaller (P < 0.0001). Diet-induced changes in Lp(a) were strongly correlated with changes in OxPL/apoB (P < 0.0001). The increases in plasma Lp(a) levels after the LFHC diet were also correlated with decreases in medium LDL particles (P < 0.01) and increases in very small LDL particles (P < 0.05). These results demonstrate that induction of increased levels of Lp(a) by an LFHC diet is associated with increases in OxPLs and with changes in LDL subclass distribution that may reflect altered metabolism of Lp(a) particles.

Comment- Pretty straight up study, and low carb wins big time. Lipoprotein a, apo B, and oxidizzed phospolipids are all important markers of heart disease, and all of them got worse on low fat, better on low carb.

SAN FRANCISCO-Although a link between nutrition and cancer was posited as long ago as ancient China, modern studies have been only partly successful in illuminating this association, explained Arthur Schatzkin, MD, DrPH, of the NCI's Nutritional Epidemiology Branch, speaking here at the American Society of Clinical Oncology Annual Meeting at a Scientific Symposium on Nutrition and Cancer.

Do we have hard, credible evidence that nutritional modification can truly affect the incidence of malignant disease in humans? The answer, in short, is a resounding maybe. We are getting there, but nutrition and cancer is a complex and difficult field. When it comes to nutrition, the evidence is softer and vulnerable to the results of the latest analysis or published paper.

The dearth of hard evidence coupled with inherent difficulties in conducting valid studies in this area has led to confusion and inconsistency about the role of nutrition in the risk of developing cancer.

Obstacles to conducting studies of nutritional epidemiology of cancer cited by Dr. Schatzkin include: exposure assessment error (is the right dietary factor being studied and are the right questions being asked?), inadequate range of exposure (many populations have narrow intake distributions for certain potentially cancer-related nutrients and foods), and confounding (people who follow a certain type of diet may also differ in biologic or lifestyle factors that are related to the risk of developing cancer).

Randomized, controlled trials largely circumvent the problem of confounding, and results from such studies are extremely compelling, Dr. Schatzkin continued. However, these studies are expensive and logistically complex to mount.

At present, Dr. Schatzkin said it is difficult to make recommendations with certainty regarding controversial areas such as the relationship of dietary fat intake and breast cancer; the role of dietary fiber and colorectal cancer; and the role of vitamins/supplements (i.e., beta carotene and lung cancer, lycopene, and prostate cancer, and folic acid and colorectal cancer). The hope is that future studies will help to resolve these issues.

But even this was only a guess. "We have attributed the largest risk to dietary factors," they wrote. "It must be emphasized the figure chosen is highly speculative and chiefly refers to dietary factors which are not yet reliably identified."

However, even by 1981 two possible preventive factors, beta-carotene and other precursors of Vitamin A, and dietary fiber were already identified. It was a satisfying overall package. Beta-carotene was an antioxidant, and there was some evidence that antioxidants might have a role in preventing the No. 1 cancer killer, lung cancer. Fiber seemed to have a preventive role in the No. 2 cancer--colorectal cancer-and eating more fiber usually meant a lower fat diet, and both animal and vegetable fats were also suspects in increasing cancer risk.

Finally, these theories nicely fit the dietary recommendations that had already been made. While the scientific literature grew to include literally hundreds of studies examining these issue from some narrow perspective, the scientists at the National Cancer Institute understood that convincing scientific evidence was going to be achieved with only one scientific technique: the randomized clinical trial.

In a clinical trial intervention study, the only meaningful difference between a treatment group and an untreated control group is the chemical or food item under study. The best studies are double blind, with neither investigator nor volunteer knowing whether they are receiving the active treatment, or a placebo.Beta-carotene on Trial

Beta-carotene was the first to be studied in such trials, but researchers used a dietary supplement pill rather than foods. The pill had a known quantity of the chemical under study, could be given in a double blind trial using a placebo, and did not involve the experimental complexities of trying to modify diet in a consistent fashion for years on end.

Enthusiasts believed that beta-carotene had wondrous powers-that it might be an antioxidant, boost the immune system, and even inhibit the formation of cancerous cells. This evidence came from bench biochemistry, experiments with cells in petri dishes, and examinations of large populations of people where many, many factors could be involved. Now this idea was being tested in a manner that might provide definitive scientific evidence of the benefit to ordinary people.

As a National Academy of Sciences panel recently noted, not one major trial of beta-carotene produced any evidence of a beneficial effect on cancer, and one study suggested a possible harmful effect. Whether beta-carotene was studied in low risk patients (22,000 practicing physicians), or among high risk asbestos workers and heavy smokers, no benefit was seen in studies of 8 to 12 years duration.Fiber and Fruit to the Test

Fiber, fruits, vegetables-the heart of the "5 a day program" --were the next to be systematically studied in clinical trials. One central problem in studying cancer is that despite it being the second ranked cause of death, cancer is quite rare in any group of healthy people and therefore requires studying literally tens of thousands for many years to acquire a few dozen cases of the specific cancer of interest.

However, colon cancer begins as benign polyps and adenomas that only later become malignant. By leaving out all the thousands of people who were not at great risk anyway, and focusing on people who already developed the earliest precursors, the investigators could learn much more about fiber in trials of only a few thousand patients.

Still the problem of modifying diet remained. In one study participants were given one of two identical-looking breakfast cereals from Kellogg that contained either 13 grams of additional fiber or just 2 grams. The second study attempted and achieved a broader dietary modification. Through training and counseling sessions, the intervention group was induced to increase fiber by 75 percent, boost their number of servings of fruits and vegetables by two thirds; and to reduce the fat in their diet. The other group was not counseled and food intake remained largely unchanged.

In both studies the intervention was foods rather than the purified chemical ingredient. In both studies real dietary changes were maintained for three to four years. Nevertheless, no effect whatever was found on the recurrence of polyps or adenomas in either study. Fiber, fruits and vegetables worked no better in preventing cancer than had beta-carotene

Fiber supplements were defined, for the purposes of this project, as fibers which have been isolated from the original source. The fiber may be incorporated into foods and beverages or taken as a pill or powder.

Two studies (Pasman, 1997; Rossner, 1987) found decreased energy intake with five grams to 40g fiber per day for one week to three months.

* Decreased energy intake o Pasman, 1997, one week each (crossover): 40g per day guar gum; one week AND four mJ with 20g guar gum or control or six mJ with 20g guar gum or control o Rossner, 1987, three months: 1,400-kcal diet with five grams per day fiber supplement (grain and citrus fiber) or placebo; two months AND 1,600-kcal diet with seven grams per day fiber supplement (vegetable, grain and citrus fiber) or placebo.

No Difference in Energy Intake

Three studies (Kovacs, 2001; Pasman and Westerterp-Plantenga, 1997; Rigaud, 1990) found no difference in energy intake in individuals that consumed 6.6g to 20g fiber supplements for two weeks to 14 months.

Five studies (Hylander, 1983; Kovacs, 2001; Pasman and Westerterp-Plantenga, 1997; Rigaud, 1990; Ryttig, 1989) found significantly less hunger or increased satiety, following consumption of fiber supplements providing six grams to 20g fiber for two weeks to 14 months.

* Less hunger or greater satiety with fiber supplements o Hylander, 1983, three weeks: 6.6g ispaghula, 6.6g bran or control o Kovacs, 2001, two weeks each diet: Breakfast replaced with solid meal or semi-solid meal with or without fiber supplement; 6.6g per day guar gum o Pasman and Westerterp-Plantenga, 1997, 14 months: 16g to 20g guar gum, 10g to 15g guar gum or control o Rigaud, 1990, six months: Seven grams per day insoluble fiber supplement (beet, barley, citrus; 90% insoluble) or placebo o Ryttig, 1989: 1,200-kcal diet with seven grams per day fiber supplement or placebo for 11 weeks, then 1,600-kcal diet with six grams per day fiber supplement or placebo for 16 weeks, then ad lib diet with six grams per day fiber supplement for 25 weeks.

No Impact on Hunger

Three studies (Adam, 2005; Pasman, 1997; Rossner, 1987) found that fiber supplements providing five grams to 40g fiber for one meal to three months had no impact on satiety or hunger in obese individuals.

* No change between groups in hunger or satiety with fiber supplements o Adam, 2005, one meal: 50g galactose with 2.5g guar gum or control at breakfast o Pasman, 1997, one week each (crossover): 40g per day guar gum; one week AND four mJ with 20g guar gum or control or six mJ with 20g guar gum or control o Rossner, 1987, three months: 1,400-kcal diet with five grams per day fiber supplement (grain and citrus fiber) or placebo; two months AND 1,600-kcal diet with seven grams per day fiber supplement (vegetable, grain and citrus fiber) or placebo.

Adam also explored the impact of fiber supplements on Glucagon-like peptide 1 (GLP-1), a gastrointestinal peptide believed to signal satiety via gastric and small bowel nerves. GLP-1 was found to be elevated with administration of 50g galactose and 2.5g guar gum, however the increase in GLP-1 was not related to ratings of satiety in obese individuals, as was seen in normal-weight individuals.

The majority of studies (Birketvedt, 2000; Pasman and Westerterp-Plantenga, 1997; Solum, 1987; Vuksan, 1999) found no difference in the change in serum lipids from control with fiber supplementation on primarily hypocaloric diets.

Improved Total Cholesterol

One study found greater improvement in total cholesterol in the group which consumed 4.5g fiber from agar for 12 weeks.

Two studies (Rossner, 1987, Ryttig, 1989) found a decrease in diastolic blood pressure (DBP) with seven to 26g dietary fiber for three to 12 months. Solum (1987) and Vuksan, 1999, found a decrease in blood pressure with six to 14g fiber for three to 12 weeks.

* Decreased blood pressure with fiber supplements o Rossner, 1987, three months: 1,400-kcal diet with five grams per day fiber supplement (grain and citrus fiber) or placebo; two months AND 1,600-kcal diet with seven grams per day fiber supplement (vegetable, grain and citrus fiber) or placebo o Ryttig, 1989: 1,200-kcal diet with seven grams per day fiber supplement or placebo for 11 weeks, then 1,600-kcal diet with six grams per day fiber supplement or placebo for 16 weeks, then ad lib diet with six grams per day fiber supplement for 25 weeks o Solum, 1987, 12 weeks: 1,200-kcal diet (25g per day dietary fiber) with six grams per day fiber supplement (grain and citrus fiber) or control o Vuksan, 1999, three weeks: Two grams per 100kcal konjac mannan fiber or two grams per 100kcal wheat bran fiber.

No Difference

Three studies (Kovacs, 2001; Maeda, 2005; Rigaud, 1990) found 4.5 to seven grams dietary supplements, for two to 30 weeks, led to no difference in the change in blood pressure from control.

For one thing, many researchers harbor doubts about the need to drive down cholesterol levels in the first place. Those doubts were strengthened on Jan. 14, when Merck and Schering-Plough (SGP) revealed results of a trial in which one popular cholesterol-lowering drug, a statin, was fortified by another, Zetia, which operates by a different mechanism. The combination did succeed in forcing down patients' cholesterol further than with just the statin alone. But even with two years of treatment, the further reductions brought no health benefit.DOING THE MATH

The second crucial point is hiding in plain sight in Pfizer's own Lipitor newspaper ad. The dramatic 36% figure has an asterisk. Read the smaller type. It says: "That means in a large clinical study, 3% of patients taking a sugar pill or placebo had a heart attack compared to 2% of patients taking Lipitor."

Now do some simple math. The numbers in that sentence mean that for every 100 people in the trial, which lasted 3 1/3 years, three people on placebos and two people on Lipitor had heart attacks. The difference credited to the drug? One fewer heart attack per 100 people. So to spare one person a heart attack, 100 people had to take Lipitor for more than three years. The other 99 got no measurable benefit. Or to put it in terms of a little-known but useful statistic, the number needed to treat (or NNT) for one person to benefit is 100.

Compare that with, say, today's standard antibiotic therapy to eradicate ulcer-causing H. pylori stomach bacteria. The NNT is 1.1. Give the drugs to 11 people, and 10 will be cured.

A low NNT is the sort of effective response many patients expect from the drugs they take. When Wright and others explain to patients without prior heart disease that only 1 in 100 is likely to benefit from taking statins for years, most are astonished. Many, like Winn, choose to opt out.

Plus, there are reasons to believe the overall benefit for many patients is even less than what the NNT score of 100 suggests. That NNT was determined in an industry-sponsored trial using carefully selected patients with multiple risk factors, which include high blood pressure or smoking. In contrast, the only large clinical trial funded by the government, rather than companies, found no statistically significant benefit at all. And because clinical trials themselves suffer from potential biases, results claiming small benefits are always uncertain, says Dr. Nortin M. Hadler, professor of medicine at the University of North Carolina at Chapel Hill and a longtime drug industry critic. "Anything over an NNT of 50 is worse than a lottery ticket; there may be no winners," he argues. Several recent scientific papers peg the NNT for statins at 250 and up for lower-risk patients, even if they take it for five years or more. "What if you put 250 people in a room and told them they would each pay $1,000 a year for a drug they would have to take every day, that many would get diarrhea and muscle pain, and that 249 would have no benefit? And that they could do just as well by exercising? How many would take that?" asks drug industry critic Dr. Jerome R. Hoffman, professor of clinical medicine at the University of California at Los Angeles.